Our previous work had identified a major protein kinase C substrate that was termed SMP because its phosphorylation was modulated by calcium binding proteins like S-100 and calmodulin. We have now purified SMP to homogeneity from rat brain. Also the regulation of SMP phosphorylation in intact cells has been investigated. Our previous work had demonstrated that protein kinase C is involved in desensitization of human chriogonadotropin (hCG)-sensitive adenylate cyclase. We have extended this work and have now shown that the responsiveness of beta-adrenergic sensitive adenylate cyclase may also be regulated by protein kinase C. Biochemical aspects of protein kinase C mediated modulation of receptor activity were further elucidated. Our previous work had identified a 94 kilodalton substrate of cyclic AMP-dependent protein kinase that was predominantly localized to cholinergic neurons. We have now purified this phosphoprotein to near homogeneity and the elucidation of its biological function is being elucidated. Our previous work had demonstrated that chronic treatment of rats with lithium produced marked changes in protein phosphorylation. We have extended this work using cultured cells and now show that lithium treatment of rats (48 hours) produces marked changes in protein kinase C activity and the phosphorylation of yet unidentified protein. The involvement of protein kinase C in the development of resistance to anti-tumor drugs in breast cancer has been investigated.